The Surprising Risks of Quitting Ozempic

Most people know that when they start a prescription for GLP-1 receptor agonists—such as Ozempic or Mounjaro—they work over time and are a long-term treatment. Stop taking GLP-1 drugs like Ozempic or Mounjaro, and many people regain at least some of the weight they’ve lost. Blood sugar levels may rise again, too. But research suggests that stopping these medications may carry another, less obvious consequence: the loss of some of the drugs’ protections against heart attack and stroke.

In a study of more than 132,000 U.S. veterans taking GLP-1 medications, researchers found that treatment offered cardiovascular benefits. But when people ceased the medications, their cardiovascular risks tended to rise. The findings, and others like them, show that while GLP-1s have many beneficial effects, they may go away when the drug itself does.

“The misconception is that I could take it for, you know, let’s say a year to lose weight,” says Ziyad Al-Aly, a nephrologist at Washington University in St. Louis, MO, who co-authored the study. “I could get off of it, and then I will still be able to maintain that cardiovascular health, or that weight loss benefit. And the fact is that these are, that GLP-1 is really a chronic treatment for a chronic condition.”

Yet staying on these medications isn’t always possible. Studies suggest that between 36 and 65 percent of people taking GLP-1s will have to stop at some point, whether they want to or not. In a 2026 survey of people who discontinued GLP-1s, more than half stopped because of cost or lack of insurance. A third stopped the drugs due to side effects like nausea and constipation. And around a quarter stopped after reaching their weight-loss goals.

The consequences of cessation may be particularly significant for people with type 2 diabetes, who are two to four times more likely to experience cardiovascular disease, including problems like heart failure, heart attack, and stroke. In Al-Aly’s study, people who continued taking GLP-1 drugs had an 18 percent lower risk of heart attack, stroke, or death compared with those taking an older diabetes treatment. It might seem like a small reduction, but “reducing the risk of stroke and cardiovascular events and major cardiovascular event, these are not a nothing burger,” he says.

But that advantage seemed to disappear after treatment stopped. Every six months, the participants who were off the drugs saw an increase in risk, back to original levels. “It takes three years to build [an] 18 percent reduction” in risk, Al-Aly says. “And 18 months of stopping to undo that.”

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But studies like Al-Aly’s are observational, says Hertzel Gerstein, an endocrinologist at McMaster University in Canada. “The people who stop the drug are not the same as the people who don't stop the drug,” he explains. The study is a record of people who started and stopped the drugs on their own—they were not assigned to do so as they would be in a study. Those who stopped taking the drugs could have higher risks to begin with, or other illnesses that are not included. “Unless you do a randomized controlled trial, you really don't know the clear answer to the question.”

Scientists still aren’t sure quite how GLP-1 drugs reduce these heart events, but “we know that [a] pretty strong component of the cardiovascular/cardiometabolic benefit of GLP-1 receptor agonists is independent of weight loss,” says John Ussher, who studies cardiometabolic disease at the University of Alberta.

The drugs can affect several pathways involved in cardiovascular disease, including inflammation and blood vessel health. “Which pathways are the dominant and key to engage to induce these protective benefits is something we are still trying to understand,” says Erin Mulvihill, a biochemist at the University of Ottawa Heart Institute in Canada. Evidence from cell and animal studies suggests that GLP-1 receptor agonists “can reduce some forms of inflammation,” she says. But “it is still unclear how these studies translate to humans.”

Researchers are also investigating how GLP-1 drugs affect the cells that line blood vessels and help repair damage. Endothelial cells, which line the inside of blood vessels, play an important role in keeping arteries and veins healthy and forming new vessels, explains David Hess, a stem cell biologist at Unity Health, University of Toronto and Western University in Ontario.

High blood sugar and cholesterol can damage these cells, while cardiometabolic disease can also reduce the number of circulating progenitor cells involved in repair. These progenitor cells are “responsible for helping the vessels heal themselves, stimulating that healing process,” he says. Harming the vessels and stopping the cells that would repair them is like metabolic disease going around, starting fires—and killing all the firefighters. GLP-1 receptor agonists, he says, could help endothelial cells stay alive and preserve the progenitor cells that help with repair. Fewer fires would start, and more firefighters would be on the job.

But take away the GLP-1 receptor agonists, and fires may break out again. “It is likely that without those mechanisms being engaged, the reduced risk for [major adverse cardiovascular events] events in people living with type 2 diabetes will dissipate over time versus someone who remains on the medication,” Ussher says.

The rebound effects of discontinuing the drugs worry Al-Aly. “I call it metabolic whiplash,” he says. “You're getting your body to actually now acclimate to less inflammation, less cholesterol, less oxidative stress. It's happy. Your heart is happy, is healthy, and all of a sudden you're saying, ‘I'm going to stop at GLP-1. I'm going to expose you to more inflammation.’”

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In animal models, fluctuations in weight—that whiplash—can “accelerate the growth of fatty plaques in the arteries,” Mulvihill says. “Weight loss independent cardio protection requires more constant receptor engagement.”

While researchers are still studying the effects on blood vessels, they better understand other changes after people stop taking GLP-1 drugs. Appetite often returns with a vengeance, and blood sugar levels can climb again, particularly in people with type 2 diabetes. The medications help regulate blood sugar by stimulating insulin release and reducing glucagon, effects that can diminish once treatment ends.

This isn’t the patient’s fault, says Kim Connelly, head of cardiology at St. Michael’s Hospital, Unity Health and the University of Toronto in Canada. A GLP-1 doesn’t cure type 2 diabetes and the metabolic conditions that accompany it. The symptoms are managed, but the condition remains. “When you stop the drugs, you know, we haven’t completely reversed the state that you’re in. So therefore, it’s not surprising that we’re going to see some rebound.”

But benefits may not disappear entirely. Around two-thirds of the weight lost from GLP-1s is regained within a year. But not all of it comes back. People tend to plateau after regaining 75 percent of what they lost. Similarly, a small study of people on tirzepatide (Mounjaro) found their hemoglobin A1c—a measure of how much sugar is attached to your red blood cells—dropped by more than two percentage points in a year. After the drug was stopped, A1c levels climbed again, though not all the way back, suggesting some benefits could remain.

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Connelly also points to earlier studies of intensive blood sugar control in which some protective effects persisted for years after treatment ended. Those studies weren’t specifically about GLP-1 drugs, but they suggest that improvements in metabolic health can sometimes have lasting benefits. “I think we’ve just got to be a little bit cautious, and this is why we need longer-term studies,” of people who have gone off the drug.

GLP-1 drugs also aren’t the only way to improve cardiovascular health. “Every major regulatory society around the world has suggested that you use a GLP-1 receptor agonist on top of appropriate lifestyle modifications, dietary changes, regular exercise,” Connelly says. Sometimes, the drug can help people get to a place where they can be more active, he explains.

But “the reality is for many people who take these medications, it is not as easy as it sounds to implement the appropriate lifestyle changes if they discontinue their therapy,” Ussher says. “For those individuals, it may be their reality that they need to continue on the medication for as long as possible.”